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Gallbladder mucosal protein secretion during development of experimental cholecystitis

  • Pancreatic And Biliary Disorders
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Abstract

The development of experimental cholecystitis produced by lysophosphatidylcholine is associated with reversal of the normal absorptive characteristics of gallbladder mucosa, resulting in the intraluminal accumulation of water, glycoprotein, and protein. The purpose of the present study was to attempt to ascertain if the protein leaks into the lumen because of the cytolytic properties of lysophosphatidylcholine or if it is due to an active secretory process and to characterize the protein produced. Experiments were performed on anesthetized cats undergoing gallbladder perfusion with and without lysophosphatidylcholine. The amount of protein in the perfusate was measured and albumin clearance from blood to gallbladder lumen was calculated with and without the administration of vesicular transport inhibitors. In separate experiments, control and lysophosphatidylcholine (LPC) produced gallbladder perfusates were collected and the protein subjected to SDS-PAGE to ascertain the nature of the protein secreted. Inhibitors of both microtubular and microfilament activity decreased the protein accumulation and clearance produced by lysophosphatidylcholine. Gallbladder white blood cell accumulation and inflammation as evaluated byβ-glucuronidase and prostaglandin E levels were not significantly altered by cytochalasin or colchicine administration. Lysophosphatidylcholine also produced significant increases in perfusate LDH levels. The protein produced was primarily a 66-kDa protein. Transfer of the protein to a nitrocellulose membrane and immunoblotting with anti-albumin antibody demonstrated that the protein was albumin. The results suggest that during the development of cholecystitis, lysophosphatidylcholine produces albumin accumulation in the gallbladder primarily by inducing an active secretory process resulting in gallbladder distension.

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References

  1. Jivegard L, Thornell E, Svanik J: Pathophysiology of acute obstructive cholecystitis: Implications for non-operative management. Br J Surg 74:1084–1086, 1987

    PubMed  Google Scholar 

  2. Kaminski DL: Arachidonic acid metabolites in hepatobiliary physiology and disease. Gastroenterology 97:781–792, 1989

    PubMed  Google Scholar 

  3. German D, Barcia J, Brems J, Merenda G, Kaminski DL: Effect of bradykinin on feline gallbladder water transport and prostanoid formation. Dig Dis Sci 34:1770–1776, 1989

    PubMed  Google Scholar 

  4. Kaminski DL, Andrus CH, German D, Deshpande YG: The role of prostanoids in the production of acute acalculous cholecystitis by platelet-activating factor. Ann Surg 212:455–461, 1990

    PubMed  Google Scholar 

  5. Kaminski DL, Daneshmand H, Dean P, Deshpande YG: Prostanoids and leukotrienes in experimental feline cholecystitis. Hepatology 11:1003–1009, 1990

    PubMed  Google Scholar 

  6. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ: Protein measurements with the Folin phenol reagent. J Biol Chem 193:265–275, 1951

    PubMed  Google Scholar 

  7. Toth JL, Harvey RC, Upadyha GA, Strasberg SM: Albumin absorption and protein secretion by the gallbladder in man and in the pig. Hepatology 12:729–737, 1990

    PubMed  Google Scholar 

  8. Gottfries A: Lysolecithin. A factor in the pathogenesis of acute cholecystitis. Acta Chir Scand 135:213–217, 1969

    PubMed  Google Scholar 

  9. Sjodahl R, Taggesson C, Wetterfors J: On the pathogenesis of acute cholecystitis. Surg Gynecol Obstet 146:199–202, 1978

    PubMed  Google Scholar 

  10. Taggesson C, Norrby S, Sjodahl R: The prerequisites for local lysolecithin formation in the human gallbladder. Scand J Gastroenterol 14:379–384, 1979

    PubMed  Google Scholar 

  11. Sjodahl R, Taggesson C, Wetterfors J: Lysolecithin-mediated inflammatory reaction in rabbit gallbladder. Acta Chir Scand 141:403–409, 1975

    PubMed  Google Scholar 

  12. Neiderhiser DH, Thornell E, Bjorck S, Svanik J: The effect of lysophosphatidyl-choline on gallbladder function in the cat. J Lab Clin Med 101:699–707, 1983

    PubMed  Google Scholar 

  13. Thornell E, Jivegard L, Bukhave K, Rask-Madsen J, Svanik J: Prostaglandin E2 formation by the gallbladder in experimental cholecystitis. Gut 27:370–373, 1986

    PubMed  Google Scholar 

  14. Weltzien HU: Cytolytic and membrane-perturbing properties of lysophosphatidyl-choline. Biochem Biophys Acta 559:259–287, 1979

    PubMed  Google Scholar 

  15. Nesterin MF, Narodetskaya RV: Capacity of the gallbladder to absorb albumin. Bull Exp Biol Med 59:23–27, 1965

    Google Scholar 

  16. John WG, Mullock BM, Hinton RH: Proteins of guinea-pig bile: Selective resorption in the gallbladder. Biosci Rep 3:389–394, 1983

    PubMed  Google Scholar 

  17. Gallinger S, Harvey PRC, Petrunka CN, Ilson RG, Strasberg SM: Biliary proteins and the nucleation defect in cholesterol cholelithiasis. Gastroenterology 92:867–875, 1987

    PubMed  Google Scholar 

  18. Cameron RS, Arvan P, Castle JD: Secretory membranes and the exocrine storage compartment.In Handbook of Physiology, Section 6: The Gastrointestinal System. SG Schultz, J Forte, BB Rauner (eds). New York Oxford, 1989, pp. 1116–1117

  19. Nevalainen TJ: Ultrastructural characteristics of tuft cells in mouse gallbladder epithelium. Acta Anat 98:210–220, 1977

    PubMed  Google Scholar 

  20. Kacich RL, Renston RH, Jones AL: Effects of cytochalasin D and colchicine on the uptake translocation and biliary secretion of horseradish peroxidase and [14C]sodium taurocholate in the rat. Gastroenterology 85:385–394, 1983

    PubMed  Google Scholar 

  21. Thomas P, O'Neil PF, Zamcheck N: The effects of colchicine and vinblastine on the biliary excretion of carcinoembryonic antigen. Hepatology 5:207–210, 1985

    PubMed  Google Scholar 

  22. Veel T, Buanes T, Grotmol T, Engeland E, Raeder MG: Colchicine blocks the effects of secretin on bile duct cell tubulovesicles and plasma membrane geometry and impairs ductular HCO3 secretion in the pig. Acta Physiol Scand 139:603–607, 1990

    PubMed  Google Scholar 

  23. Bulkley GB, Kvietys PR, Parks DA, Perry MA, Granger DN: Relationship of blood flow and oxygen consumption to ischemic injury in the canine small intestine. Gastroenterology 89:852–857, 1985

    PubMed  Google Scholar 

  24. O'Leary DP, Murray FE, Turner BS, Lamont JT: Bile salts stimulate glycoprotein release by guinea pig gallbladderin vitro. Hepatology 13:957–961, 1991

    PubMed  Google Scholar 

  25. Ammendola G, DiRosa M, Sorrentino L: Leucocyte migration and lysosomal enzymes release in rat carrageenin pleurisy. Agents Actions 5:250–255, 1975

    PubMed  Google Scholar 

  26. Ohno K, Fujimoto M, Hirata M: Protective effect of prostaglandin A2 against Menadione-induced cell injury in cultured porcine aorta endothelial cells. Chem Biol Interact 78:67–75, 1991

    PubMed  Google Scholar 

  27. Kaminski DL, Deshpande YG, Westfall S, Herbold D: Evaluation of prostacyclin production by human gallbladder. Arch Surg 124:277–280, 1989

    PubMed  Google Scholar 

  28. Kaminski DL, Deshpande Y, Thomas L, Qualy J, Blank W: Effect of oral ibuprofen on formation of prostaglandins E and F by human gallbladder muscle and mucosa. Dig Dis Sci 30:933–940, 1985

    PubMed  Google Scholar 

  29. Laemmli UK: Cleavage of structural proteins during the assembly of the head of the bacteriophage T4. Nature 227:680–685, 1970

    PubMed  Google Scholar 

  30. Matsadaira PT, Burgess DR: SDS microslab linear gradient polyacrylamide gel electrophoresis. Anal Biochem 87:386–396, 1978

    PubMed  Google Scholar 

  31. Offner GD, Gong D, Afdahl NH: Identification of a 130-kilodalton human biliary concanavalin A binding protein as aminopeptidase N. Gastroenterology 106:755–762, 1994

    PubMed  Google Scholar 

  32. Towbin H, Staehlein T, Gordon J: Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: Procedure and some applications. Proc Natl Acad Sci USA 76:4350–4354, 1979

    PubMed  Google Scholar 

  33. Usumoto R, Okada Y, Tsuji T: Effect of proton pump inhibitor, omeprazole, on expression of rat parietal cell specific carbohydrate antigen, type 2 chainN-acetyllactosamine. Dig Dis Sci 39:169–176, 1994

    PubMed  Google Scholar 

  34. Neiderhiser DH, Morningstar WA, Roth HP: Absorption of lecithin and lysolecithin by the gallbladder. J Lab Clin Med 82:891–899, 1973

    PubMed  Google Scholar 

  35. Specian RD, Neurtra MR: Cytoskeleton of intestinal goblet cells in rabbit and monkey. Gastroenterology 87:1313–1325, 1984

    PubMed  Google Scholar 

  36. Kolset SO, Tolleshaug H, Berg T: The effects of colchicine and cytochalasin B on uptake and degradation of asialoglycoproteins in isolated rat hepatocytes. Exp Cell Res 122:159–167, 1979

    PubMed  Google Scholar 

  37. Bentzel CH, Hainau B, Ho S, Hui SW, Edelman T, Anagnostipoulos T, Beneditt EL: Cytoplasmic regulation of tight junction permeability: effect of plant cytokinins. Am J Physiol 239(Cell Physiol 8):C75-C89, 1980

    PubMed  Google Scholar 

  38. Madara JL: Intestinal absorptive cell tight junctions are linked to cytoskeleton. Am J Physiol 253(Cell Physiol 22):C171-C175, 1987

    PubMed  Google Scholar 

  39. Ghio AJ, Kennedy TP, Hatch GE, Tepper JS: Reduction of neutrophil influx diminishes lung injury and mortality following phosgene inhalation. J Appl Physiol 71:657–665, 1991

    PubMed  Google Scholar 

  40. Domschke W, Domschke S, Horning D, Demling L: Prostaglandin-stimulated gastric mucus secretion in man. Acta Hepato-Gastroenterol 25:292–294, 1979

    Google Scholar 

  41. Allen A, Garner A, Hunter AC, Keogh JP: The gastroduodenal mucus barrier and the place of eicosanoids.In The Eicosanoids and the Gastrointestinal Tract. K Hillier, (ed). Lancaster UK, MTP, 1988, pp. 195–213

    Google Scholar 

  42. LaMorte WW, LaMonte JT, Hale W, Booker ML, Scott TE, Turner B: Gallbladder prostaglandins and lysophospholipids as mediators of mucin secretion during cholelithiasis. Am J Physiol 251:G701-G709, 1986

    PubMed  Google Scholar 

  43. Goldman G, Kahn PJ, Alon R, Wiznitzer T: Biliary colic treatment and acute cholecystitis prevention by prostaglandin inhibitor. Dig Dis Sci 34:809–811, 1989

    PubMed  Google Scholar 

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Authors and Affiliations

  1. From the Department of Surgery, St. Louis University Hospital, 3635 Vista Avenue at Grand Boulevard, P.O. Box 15250, 63110-0250, St. Louis, Missouri

    Donald L. Kaminski MD, Yashwant G. Deshpande MS, Al Li PhD, Frances Dysart MD & Mihir Nag PhD

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  1. Donald L. Kaminski MD
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  2. Yashwant G. Deshpande MS
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  3. Al Li PhD
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  4. Frances Dysart MD
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Kaminski, D.L., Deshpande, Y.G., Li, A. et al. Gallbladder mucosal protein secretion during development of experimental cholecystitis. Digest Dis Sci 40, 1157–1164 (1995). https://doi.org/10.1007/BF02064215

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  • DOI: https://doi.org/10.1007/BF02064215

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